Magnesium-Catalyzed Asymmetric Direct Aldol Addition of Ethyl Diazoacetate to Aromatic, Aliphatic, and α,β-Unsaturated Aldehydes

Abstract

Magnesium-catalyzed enantioselective aldol between ethyl diazoacetate and aromatic, aliphatic, and α,β-unsaturated aldehydes affords α-diazo-β-hydroxy-esters in high enantioselectivities. Aldol adducts resulting from this asymmetric transformation are versatile intermediates towards the synthesis of several ester containing chiral building blocks.

Development of the Enantioselective Addition of Ethyl Diazoacetate to Aldehydes: Asymmetric Synthesis of 1,2-Diols

“…Herein we describe our efforts towards developing such a process, a portion of which has appeared in a preliminary communication, and the elaboration of such adducts for the asymmetric synthesis of vicinal diol motifs. 6 …”

“…6 At the outset, we recognized the conversion of β-hydroxy-α-diazo esters 4 to β-hydroxy-α-ketoester electrophiles A and the subsequent addition of carbon nucleophiles to such reactive intermediates with high chirality transfer could prove to be challenging due to the high propensity of these electrophiles to undergo competitive enolization or an α-ketol rearrangement. 7 Furthermore, accessibility of the resulting 1,2-diols without recourse to protecting group manipulation would rely upon the identification of carbon nucleophiles that are compatible with a free alcohol.…”

Synthesis of Microbial Signaling Molecules and Their Stereochemistry-Activity Relationships

“…55) A zinc-catalyzed asymmetric diazo addition to an imine and Noyori's asymmetric transfer hydrogenation 56) were employed to construct the stereogenic centers of the homoserine lactone and the acyl side chain respectively. The catalyst generated from (S,S)-ProPhenol and Et 2 Zn developed by Trost and co-workers 57) was treated with ethyl diazoacetate (43) and imine 42 to afford 44 stereoselectively (92:8).…”

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

“…This substitution can be effected in the presence of a base or starting from the metalated diazo compound, and leaves the diazo function intact [4]. Among the reported transformations are substitutions of the diazomethyl hydrogen for electrophiles based on boron [5–7], nitrogen (NO 2 + ) [8–12], silicon [13–15], phosphorous [16–18], sulfur [19–21] and halogens [10,22–30], as well as carbon, e.g., in aldol reactions with aldehydes [31–32], ketones [33–34] and imines [35–36]. …”